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Background: The prognostic significance of minimal residual disease (MRD) status before autologous hematopoietic stem cell transplantation (autoHCT) in patients with multiple myeloma (MM) has not been clearly elucidated. Methods: Retrospective single‐center study of adult MM patients who achieved ≥very good partial response (VGPR) after induction therapy from 2015 to 2021 received upfront autoHCT and had available pretransplant MRD status by next‐generation flow cytometry. The cohort was divided into pretransplant MRD‐negative (MRDneg) and MRD‐positive (MRDpos) groups. Results: A total of 733 patients were included in our analysis; 425 were MRDneg and 308 MRDpos at autoHCT. In the MRDpos group, more patients had high‐risk cytogenetic abnormalities (48% vs. 38%, respectively; p =.025), whereas fewer patients achieved ≥CR before autoHCT (14% vs. 40%; p <.001). At day 100 after autoHCT, 37% of the MRDpos versus 71% of the MRDneg achieved ≥CR, and at best posttransplant response 65% versus 88% achieved ≥CR, respectively. After a median follow‐up of 27.6 months (range, 0.7–82.3), the median PFS was significantly shorter for patients in the MRDpos group compared to the MRDneg group: 48.2 months (95% confidence interval [CI], 0.3–80.5) versus 80.1 months (95% CI, 0.5–80.1), respectively (p <.001). There was no significant difference in overall survival between the two groups (p =.41). Pretransplant MRDpos status was predictive of shorter PFS in multivariate analysis (hazard ratio, 1.80; 95% CI, 1.31–2.46; p <.001). The impact of pretransplant MRD status was retained in most of the examined subgroups. Conclusions: In patients achieving ≥VGPR to induction, pretransplant MRDpos status was associated with a lower CR rate after autoHCT and a shorter PFS. This retrospective single‐center study evaluated the prognostic impact of pretransplant minimal residual disease (MRD) status by next‐generation flow cytometry in 733 multiple myeloma patients who achieved ≥ very good partial response after induction therapy and received upfront autologous hematopoietic stem cell transplantation (autoHCT). Pretransplant MRD positivity was associated with a lower complete remission rate after autoHCT and a shorter progression‐free survival. [ABSTRACT FROM AUTHOR]

While the body of research on grand challenges (GCs) has grown, our understanding of the role of corporate social innovation (CSI) in tackling exigent GCs, such as the COVID‐19 pandemic, is limited. Based on in‐depth analyses of four cases of CSI in the services sector during the COVID‐19 pandemic, this paper contributes to the GC literature by developing a 3Es framework of the CSI process (i.e., embeddedness, engagement, and enhancement) to illustrate the mechanisms through which exigent GCs can be effectively addressed by firms in the services sector. First, CSI embeddedness in intersectoral partnerships with international organizations based on deep‐rooted trust and collective commitment is found to be a fundamental mechanism for efficiently addressing the COVID‐19 crisis. Second, CSI engagement through the transformation of existing technology and/or the adaption of existing products/services is found to be an important mechanism for meeting pandemic‐induced social needs. Specifically, it is found that leading‐edge technologies such as digital platforms can be rapidly repurposed to enable loosely coupled systems that evolve as a new channel to bring together various stakeholders and thus address this urgent GC. Finally, CSI enhancement supported by managerial agility and participatory governance structure plays a crucial role in enabling CSI to function effectively in the context of exigent GCs. [ABSTRACT FROM AUTHOR]

Ticks are ectoparasites that cause dermatologic reactions directly by their bites and indirectly as vectors of bacterial, protozoal and viral diseases. Consequences vary from minor local reactions to significant systemic sequelae and are therefore of clinical relevance to dermatologists. In this article, Australian ticks of medical importance are reviewed through the lens of dermatology. [ABSTRACT FROM AUTHOR]

Microtubules have been an attractive target of cancer drug discovery due to their highly dynamic nature during mitosis. Griseofulvin, a natural antifungal compound, is known to interfere with microtubule dynamics. In the present study, we prepared and analyzed twenty‐seven novel griseofulvin derivatives. Three of these compounds had GI50 values <10 μM (5.74 to 9.7 μM) in breast cancer cell line CAL‐51. The most promising compound ((2S,6'R)‐4'‐(benzhydrylamino)‐7‐chloro‐4,6‐dimethoxy‐6'‐methyl‐3H‐spiro[benzofuran‐2,1'‐cyclohexan]‐3'‐ene‐2',3‐dione), was characterized as a microtubule‐stabilizing agent with a GI50 value of 5.74±1.43 μM compared to 10.79±3.06 μM GI50 for parental griseofulvin. It also inhibited the proliferation of other cancer cell lines, including KB‐3‐1 and HCT116, with GI50 values of 1.19±0.34 μM and 2.48±0.40 μM, respectively. Treatment of cancer cells with it resulted in aberrant mitosis causing G2/M arrest. Finally, we show that this compound increased the expression of p53 protein and induced apoptotic cell death. [ABSTRACT FROM AUTHOR]

DNA damage is a causative factor in ageing of the vasculature and other organs. One of the most important vascular ageing features is reduced nitric oxide (NO)soluble guanylate cyclase (sGC)—cyclic guanosine monophosphate (cGMP) signaling. We hypothesized that the restoration of NO‐sGC‐cGMP signaling with an sGC activator (BAY 54–6544) may have beneficial effects on vascular ageing and premature death in DNA repair‐defective mice undergoing accelerated ageing. Eight weeks of treatment with a non‐pressor dosage of BAY 54–6544 restored the decreased in vivo microvascular cutaneous perfusion in progeroid Ercc1∆/− mice to the level of wild‐type mice. In addition, BAY 54–6544 increased survival of Ercc1∆/− mice. In isolated Ercc1∆/− aorta, the decreased endothelium‐independent vasodilation was restored after chronic BAY 54–6544 treatment. Senescence markers p16 and p21, and markers of inflammation, including Ccl2, Il6 in aorta and liver, and circulating IL‐6 and TNF‐α were increased in Ercc1∆/−, which was lowered by the treatment. Expression of antioxidant genes, including Cyb5r3 and Nqo1, was favorably changed by chronic BAY 54–6544 treatment. In summary, BAY 54–6544 treatment improved the vascular function and survival rates in mice with accelerated ageing, which may have implication in prolonging health span in progeria and normal ageing. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) incidence is increasing in our region. There is no specific CRC control programme or national cancer registry in Pakistan. Previously, no data have been published on presentation delay and diagnosis delay of CRC in our region. This study is conducted to determine the factors affecting delay in presentation and diagnosis and to provide baseline information to launch a CRC control programme. The primary objective is to determine factors causing delay in diagnosis of CRC. The secondary objective is to evaluate the relationship between tumour site and stage of CRC with presenting symptoms and symptom duration. Methods: This project is a prospective cross‐sectional study on 113 biopsy‐proven CRC patients admitted to the surgical ward of Civil Hospital Karachi. Results: The total number of participants was 113. Presentation delay was observed in 83.2% of patients. The main reasons for a reported delay in the presentation were lack of patients' knowledge that these symptoms may be cancer (60.4%), the wrong diagnosis by the primary physician (34.6%) or the patient did not want to visit the doctor (0.04%). Most tumours (95%) originated from the sigmoid and rectum; 44.2% and 38.9% of the patients were diagnosed at Stages 3 and 4, respectively. Conclusions: This study revealed that CRC patients in Pakistan are facing delays in presentation and diagnosis. This is the reason behind diagnosis at the advanced stage with a poor prognosis. On the basis of this study findings, CRC control programme should be introduced to detect CRC at an early stage. [ABSTRACT FROM AUTHOR]

Community‐acquired pneumonia (CAP) is a major cause of sepsis. Despite several clinical trials targeting components of the inflammatory response, no specific treatment other than antimicrobial therapy has been approved. This argued for a deeper understanding of sepsis immunopathology, in particular factors that can modulate the host response. Small non‐coding RNA, for example, micro (mi)RNA, have been established as important modifiers of cellular phenotypes. Notably, miRNAs are not exclusive to the intracellular milieu but have also been detected extracellular in the circulation with functional consequences. Here, we sought to determine shifts in circulatory small RNA levels of critically ill patients with CAP‐associated sepsis and to determine the influence of clinical severity and causal pathogens on small RNA levels. Blood plasma was collected from 13 critically ill patients with sepsis caused by CAP on intensive care unit admission and from 5 non‐infectious control participants. Plasma small RNA‐sequencing identified significantly altered levels of primarily mature miRNAs in CAP relative to controls. Pathways analysis of high or low abundance miRNA identified various over‐represented cellular biological pathways. Analysis of small RNA levels against common clinical severity and inflammatory parameters indices showed direct and indirect correlations. Additionally, variance of plasma small RNA levels in CAP patients may be explained, at least in part, by differences in causal pathogens. Small nuclear RNA levels were specifically altered in CAP due to Influenza infection in contrast to Streptococcus pneumoniae infection. Pathway analysis of plasma miRNA signatures unique to Influenza or Streptococcus pneumoniae infections showed enrichment for specific proteoglycan, cell cycle, and immunometabolic pathways. [ABSTRACT FROM AUTHOR]

Global health estimates indicated approximately 322 million people living with depression. Rising cost of depressive illness treatment and non‐responsiveness to existing therapies demand continued research to explore new and more potent therapies. Exploring the potential of natural compounds for their potent antidepressant potentials is becoming topic of interest for scientists. Anti‐inflammatory activity of thymoquinone, the active ingredient of Nigella sativa, has been well documented. Current study tested thymoquinone for its antidepressant effect in a Concanavalin A (Con A)‐induced depressive‐like behavior in BALB/c mice. Thymoquinone successfully protected against Con A‐induced behavioral despair and anxiety‐like behavior. Reduced grooming behavior as a function of Con A treatment, was also reinstated. Underlying mechanism responsible for antidepressant activity of thymoquinone was analyzed by molecular docking. Thymoquinone interacts in halogen‐binding pocket (HBP) of serotonin reuptake transporter indicating its potential as serotonin reuptake inhibitor. Results of current study anticipate thymoquinone as a potential antidepressant drug candidate. Practical applications: Black seeds of Nigella sativa are consumed with traditional and religious reference since centuries. Thymoquinone, active, and abundant component of Nigella sativa, has shown positive effects in multiple studies against arthritis, asthma, hepatic injury, neurodegeneration, and cancer owing to its immunomodulatory and anti‐inflammatory attributes. Considering inflammation as one of central components involved in pathophysiology of major depressive disorder, thymoquinone has been evaluated in current study for its antidepressant potential. Positive results of current study propose thymoquinone as an affordable, natural antidepressant drug candidate with better safety profile than currently available antidepressant regimes. Thymoquinone might provide benefits against inflammation‐related sickness behavior that is associated with poorer outcome of clinical depression, thus, paving the way for effective drug development against treatment‐resistant depression. [ABSTRACT FROM AUTHOR]

A 56‐year‐old woman with hypohidrotic ectodermal dysplasia presented with a 10‐year history of persisting wart‐like skin lesions on her feet. Biopsy revealed changes of eccrine syringofibroadenoma. These lesions are rare, with only nine case reports describing an association with ectodermal dysplasia of hidrotic type (Clouston and Schopf's syndrome). To our knowledge, this is the first case of eccrine syringofibroadenoma developing in the hypohidrotic/anhidrotic subtype of ectodermal dysplasia. [ABSTRACT FROM AUTHOR]

This study proposes EWMA-type control charts by considering some auxiliary information. The ratio estimation technique for the mean with ranked set sampling design is used in designing the control structure of the proposed charts. We have developed EWMA control charts using two exponential ratio-type estimators based on ranked set sampling for the process mean to obtain specific ARLs, being suitable when small process shifts are of interest. [ABSTRACT FROM AUTHOR]

Country of origin (COO) effects with respect to price, quality, brand effect, and social status to determine elite consumers' buying behavior in the emerging market of Pakistan are investigated. Manufacturers are looking for new consumers with a resilient purchasing power, which is likely to grow, in emergent markets. The most important finding resulting from the present research is the relatively limited significance that COO effects have on product perceptions and on the buying behavior of an elite, affluent group of consumers. The research demonstrated that COO effects, while important, do not often dominate the process of consumer preference formation or the decision to buy. This finding stands in marked contrast to earlier research. The equal importance of specific cue information with COO information when making purchase decisions is emphasized by the significant correlations between some responses to COO, price, quality, brand effect, and social status items. © 2008 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The article explores the impact of body mass index (BMI) on outcomes of multiple myeloma patients undergoing upfront autologous stem cell transplant. The study included a large cohort of patients with varying BMIs and analyzed progression-free survival, overall survival, haematological response, and measurable residual disease status. The findings suggest that elevated BMI did not adversely affect survival outcomes, including in patients with severe obesity, indicating that BMI may not significantly impact eligibility for auto-HCT in multiple myeloma patients. The study acknowledges limitations of retrospective analysis but provides valuable insights into the relationship between BMI and treatment outcomes in this patient population. [Extracted from the article]

Keloid is characterized by benign overgrowth of dermal collagen in response to skin injury in genetically predisposed individuals. Intralesional triamcinolone and bleomycin have been used with varying success in the treatment of keloids. To compare the efficacy of intralesional triamcinolone versus intralesional bleomycin in the treatment keloids. A total of 164 patients were randomized into two of 82 each. Group A received intralesional bleomycine and Group B received intralesional triamcinolone. Patients were scored at baseline and at the end of treatment for therapeutic response based on reduction on patient and observer scar assessment scale (POSAS). Mean baseline POSAS score was 91 ± 10.98 SD check in Group A and 90 ± 10.85 SD in Group B. POSAS score after 24 weeks 26 SD ± 11.91 in Group and 34 ± 12.28 in Group B. This difference was statistically difference. Intralesional bleomycin is more efficacious than intralesional triamcinolone acetonide in the treatment of keloids. [ABSTRACT FROM AUTHOR]